title: Genomic heterogeneity of translocation renal cell carcinoma.
abstract: OBJECTIVE
  Translocation renal cell carcinoma (tRCC) is a rare subtype of kidney cancer involving the TFEB/TFE3 genes. We aimed to investigate the genomic and epigenetic features of this entity.
  
  
  METHODS
  Cytogenomic analysis was conducted with 250K single-nucleotide polymorphism microarrays on 16 tumor specimens and four cell lines. LINE-1 methylation, a surrogate marker of DNA methylation, was conducted on 27 cases using pyrosequencing.
  
  
  RESULTS
  tRCC showed cytogenomic heterogeneity, with 31.2% and 18.7% of cases presenting similarities with clear-cell and papillary RCC profiles, respectively. The most common alteration was a 17q gain in seven tumors (44%), followed by a 9p loss in six cases (37%). Less frequent were losses of 3p and 17p in five cases (31%) each. Patients with 17q gain were older (P=0.0006), displayed more genetic alterations (P<0.003), and had a worse outcome (P=0.002) than patients without it. Analysis comparing gene-expression profiling of a subset of tumors bearing 17q gain and those without suggest large-scale dosage effects and TP53 haploinsufficiency without any somatic TP53 mutation identified. Cell line-based cytogenetic studies revealed that 17q gain can be related to isochromosome 17 and/or to multiple translocations occurring around 17q breakpoints. Finally, LINE-1 methylation was lower in tRCC tumors from adults compared with tumors from young patients (71.1% vs. 76.7%; P=0.02).
  
  
  CONCLUSIONS
  Our results reveal genomic heterogeneity of tRCC with similarities to other renal tumor subtypes and raise important questions about the role of TFEB/TFE3 translocations and other chromosomal imbalances in tRCC biology.
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Gabriel G
authors.initials: GG
authors.lastname: Malouf
authors.affiliation: Departments of Pathology & Immunology and Human & Molecular Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Federico A
authors.initials: FA
authors.lastname: Monzon
authors.affiliation: Department of Genetics and INSERM U830, Institut Curie, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Couturier
authors.affiliation: Department of Pathology, Hôpital Saint Joseph, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Molinié
authors.affiliation: Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
authors.affiliation: Department of Pathology, Hôpital Foch, Suresnes, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Camparo
authors.affiliation: Department of Bioinformatics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Bioinformatics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Hui
authors.initials: H
authors.lastname: Yao
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Pheroze
authors.initials: P
authors.lastname: Tamboli
authors.affiliation: Department of Pathology, Texas Children's Hospital, Houston, Texas.
authors.forename: Dolores
authors.initials: D
authors.lastname: Lopez-Terrada
authors.affiliation: Department of Pathology, Loyola University Hospital, Chicago, Illinois.
authors.forename: Maria
authors.initials: M
authors.lastname: Picken
authors.affiliation: Departments of Medicine and Pathology, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Marileila
authors.initials: M
authors.lastname: Garcia
authors.affiliation: Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Asha S
authors.initials: AS
authors.lastname: Multani
authors.affiliation: Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sen
authors.initials: S
authors.lastname: Pathak
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Wood
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Nizar M
authors.initials: NM
authors.lastname: Tannir
mesh_terms: D000293:Adolescent; D000328:Adult; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D014178:Translocation, Genetic / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C064972:TFEB protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53